Pethidine and Related 4-Phenylpiperidine Analgesics

Casy, A. F.; Parfitt, Robert T.

doi:10.1007/978-1-4899-0585-7_6

Cited by 2 publications

(2 citation statements)

References 80 publications

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“…Initial studies investigated the effects of N -substitution on meperidine and results showed that N -phenylbutylnormeperidine was not a P-gp substrate in vitro [78]. Additionally, this compound was previously reported as twice the potency of meperidine [79] making it a good lead compound to test our hypothesis that opioids which lack P-gp substrate activity would not induce opioid tolerance. A series of 3- and 6-desoxymorphine analogs was also investigated, resulting in the finding that removal of the 3- and/or 6-OH group generally decreased in vitro P-gp substrate activity; 6-desoxymorphine was chosen as the lead compound from this series since it has about 10x the potency of morphine and it lacked in vitro P-gp substrate activity [80].…”

Section: Development Of Opioid Analgesics Lacking P-gp Substrate Actimentioning

confidence: 99%

Opioid Analgesics and P-Glycoprotein Efflux Transporters: A Potential Systems-Level Contribution to Analgesic Tolerance

Mercer¹,

Coop²

2011

CTMC

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Chronic clinical pain remains poorly treated. Despite attempts to develop novel analgesic agents, opioids remain the standard analgesics of choice in the clinical management of chronic and severe pain. However, mu opioid analgesics have undesired side effects including, but not limited to, respiratory depression, physical dependence and tolerance. A growing body of evidence suggests that P-glycoprotein (P-gp), an efflux transporter, may contribute a systems-level approach to the development of opioid tolerance. Herein, we describe current in vitro and in vivo methodology available to analyze interactions between opioids and P-gp and critically analyze P-gp data associated with six commonly used mu opioids to include morphine, methadone, loperamide, meperidine, oxycodone, and fentanyl. Recent studies focused on the development of opioids lacking P-gp substrate activity are explored, concentrating on structure-activity relationship development to develop an optimal opioid analgesic lacking this systems-level contribution to tolerance development. Continued work in this area will potentially allow for delineation of the mechanism responsible for opioid-related P-gp up-regulation and provide further support for evidence based medicine supporting clinical opioid rotation.

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Section: Development Of Opioid Analgesics Lacking P-gp Substrate Actimentioning

confidence: 99%

Opioid Analgesics and P-Glycoprotein Efflux Transporters: A Potential Systems-Level Contribution to Analgesic Tolerance

Mercer¹,

Coop²

2011

CTMC

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“…Pethidine is metabolized in the liver where it is extensively degraded by N-demethylation to norpethidine and by hydrolysis to pethidinic acid. The elimination half-life of pethidine is 3 to 6 h. The metabolites are excreted by the kidney in the free form and as conjugates with glucuronic acid 21 . The half-life of norpethidine is approximately 15 h, but this may be increased up to 35 h in patients with renal failure 22 .…”

Section: Historymentioning

confidence: 99%

Epidural Pethidine: Pharmacology and Clinical Experience

Kee

1998

Anaesth Intensive Care

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Pethidine is an effective epidural opioid for the treatment of acute pain. Its use has been well described in Australian and New Zealand practice, particularly in the field of obstetric anaesthesia. Reported methods of delivery have included bolus injection, continuous infusion and patient-controlled epidural analgesia. Areas of application have included treatment of postoperative pain, labour pain and intraoperative pain. Because of its intermediate lipid solubility, pethidine may have advantages over many other epidural opioids. However, potential for accumulation of norpethidine limits its use to relatively short durations of treatment.

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Pethidine and Related 4-Phenylpiperidine Analgesics

Cited by 2 publications

References 80 publications

Opioid Analgesics and P-Glycoprotein Efflux Transporters: A Potential Systems-Level Contribution to Analgesic Tolerance

Opioid Analgesics and P-Glycoprotein Efflux Transporters: A Potential Systems-Level Contribution to Analgesic Tolerance

Epidural Pethidine: Pharmacology and Clinical Experience

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